Eye Diseases Commons^™

Pentosan Polysulfate Sodium (Pps, Elmiron) Maculopathy Demonstrates The Importance Of Coordinated Care From A Low Vision Perspective, Charlotte I. Spada Od, Stephanie Schmiedecke Barbieri Od, Patricia Sanchez Diaz Dvm, Phd, Jeffrey Rabin Od, Phd

Optometric Clinical Practice

Background: Pentosan polysulfate sodium (PPS, Elmiron®) is a widely used medication to reduce pain caused by interstitial cystitis, a bladder disorder most often affecting females. PPS maculopathy is a novel form of toxic retinal disease often not recognized or mistaken for other retinal conditions such as macular degeneration due to the initial similarities on fundus exam. However, when visualized using fundus autofluorescence, affected eyes show characteristic hyper/hypo-autofluorescent patterns.

Case report: A patient taking PPS for 10 years presented with macular changes and complaints of blurry vision and nyctalopia. Clinical, electrodiagnostic, and genetic testing were performed including fundus autofluorescence and …

Gene-Agnostic Therapeutic Strategies For Inherited Retinal Diseases: Neuroprotection And Immunomodulation, Lucas W. Rowe, S. Patricia Becerra, Robert E. Maclaren, Robert L. Avery, Charles C. Wykoff, Allen C. Ho, Carl D. Regillo, Dean Eliott, Andrew Osborne, Katie M. Binley, Thomas A. Ciulla

Wills Eye Hospital Papers

Background/Objectives: Inherited retinal diseases (IRDs) represent a genetically heterogeneous group of disorders caused by mutations in over 280 genes with more than 3100 identified variants. While gene-specific replacement therapies have achieved landmark success with voretigene neparvovec (Luxturna) for biallelic RPE65-associated retinal dystrophy, developing individual therapies for each genetic subtype remains impractical. This review examines gene-agnostic therapeutic approaches utilizing neuroprotection and immunomodulation that target common pathophysiological mechanisms shared across multiple IRD genotypes. Methods: We reviewed the literature on neuroprotective and immunomodulatory gene therapy strategies for IRDs, focusing on neurotrophic factors and complement system modulation. Results: Neuroprotective approaches delivering neurotrophic factors—including pigment …

Infectious Retinitis Associated With Jak Inhibitors: The Ongoing Duality Of Jak Inhibitors, Jose S. Pulido, Fukutaro Mano, Marcello Casella, Susumu Ishida

Wills Eye Hospital Papers

PURPOSE: To discuss the recent evidence that Janus kinase (JAK) inhibitors can cause viral retinitis.

METHODS: A commentary on the case report in this issue and a review of cases in the literature.

RESULTS: A total of 6 cases have now been reported of cytomegalovirus retinitis associated with Jak inhibitors. Additionally, there was a case of bilateral toxoplasma retinitis and a case of herpetic scleritis.

DISCUSSION: It is important to be aware of the potential blinding complications associated with JAK inhibitors and if the patient complains of acute vision loss and/or floaters, the patient should be emergently referred to a …

Ornithine Metabolism In Retinal Pigment Epithelium And Retina And Implications In Gyrate Atrophy, Artjola Puja

Graduate Theses, Dissertations, and Problem Reports (ETD)

Ornithine aminotransferase (OAT) is a mitochondrial enzyme that regulates ornithine metabolism by converting ornithine to pyrroline-5-carboxylate, a precursor for proline and glutamate synthesis. Deficiency of OAT causes systemic ornithine accumulation and leads to gyrate atrophy (GA) of the choroid and retina, a hereditary disorder characterized by progressive chorioretinal degeneration and irreversible vision loss. Chorioretinal atrophy typically starts at the mid-peripheral retina and progresses toward the macula. Although elevated ornithine is considered toxic to the eye, how ornithine is metabolized in ocular tissues and why OAT deficiency causes selective, region-specific vulnerability remain unclear. We combined ex vivo and in vivo stable …

A Comprehensive Study Of C-Kit-Expressing Amacrine Cells In The Mammalian Retina, Zheng Jiang, Wen Shen

Faculty, Staff and Students Publications

Amacrine cells assemble complex circuits in the inner retina, where they integrate, modulate, and relay spatial and temporal information to retinal ganglion cells. Nevertheless, their organization and functional diversity are still not fully understood. In this study, we identify a distinct group of amacrine cells that express the stem cell factor receptor-c-Kit. Using combined techniques of anti-CD117 (c-Kit) immunolabeling, confocal imaging, and computational algorithms, we characterize the morphological features and spatial distribution of the c-Kit-expressing amacrine cells. Our results show that c-Kit-expressing amacrine cells are GABA-positive neurons with medium to wide dendritic fields that stratify within the specific strata in …

Generation Of Ipscs (Rfsci007-A, Rfsci008-A) From A Patient With Early-Onset Bilateral Drusen And A Healthy Sibling For Retinal Disease Modeling, Sonali Singh, Wendy Runyon, Sam Hu, Paige Grona Kennedy, Ajeet Singh, Rinki Ratnapriya, Ritu Kumar, Karl Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Drusen are extracellular deposits between the retinal pigment epithelium and Bruch's membrane, commonly linked to age-related macular degeneration (AMD). However, their presence in younger individuals offers a unique opportunity to study early disease mechanisms before extensive degeneration. We generated two human induced pluripotent stem cell (hiPSC) lines from siblings' peripheral blood mononuclear cells-one with early-onset bilateral drusen and the other unaffected. This genetically matched iPSC pair enables investigation of early drusen associated pathological changes driving retinal disease development.

Derivation Of Pluripotent Stem Cell Lines (Rfsci005-A, Rfsci006-A) From Siblings Harboring Identical High-Risk Complement Variants With Discordant Age-Related Macular Degeneration, Naresh Rajendran, Ajeet Singh, Wendy Runyon, Sam Hu, Ritu Kumar, Rinki Ratnapriya, Karl Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Age-related macular degeneration (AMD) is a complex disease influenced by genetic and environmental factors. Variants in the complement pathway, especially in the CFH gene, increase AMD risk, yet disease severity can differ among individuals with identical high-risk genotypes. We generated induced pluripotent stem cell (iPSC) lines from siblings carrying identical high-risk complement variants but displaying discordant AMD phenotypes. These lines provide a unique platform to study epigenetic, transcriptomic, and environmental factors driving AMD heterogeneity. By comparing differentiated retinal cells, we aim to reveal mechanisms behind variable disease susceptibility and inform personalized therapies for AMD.

Delphi Panel On Neuromodulation As A Treatment Strategy For Dry Eye Disease: Unlocking The Potential Of Natural Tear Production, Esen Akpek, Lyndon Jones, Kelly K Nichols, Lisa M Nijm, Stephen Pflugfelder

Faculty, Staff and Students Publications

Purpose: Chronic tear deficiency, through reduced production and/or increased evaporation, is regarded as a root cause of dry eye disease (DED). The goal of treating DED is restoration of the tear film ultimately resulting in ocular surface homeostasis. Multiple therapeutic prescription drugs to manage DED exist with varying speed of onset, overall magnitude of efficacy, and tolerability. Neuromodulation is an emerging treatment modality offering direct stimulation of natural tear production. A modified Delphi study was conducted to explore the role of neuromodulation as a treatment for DED.

Methods: Twenty DED experts participated in three rounds of structured electronic Delphi questionnaires. …

Image-Based Meta- And Mega-Analysis (Ibmma): A Unified Framework For Large-Scale, Multi-Site, Neuroimaging Data Analysis, Nick Steele, Ashley A Huggins, Rajendra A Morey, Ahmed Hussain, Courtney Russell, Benjamin Suarez-Jimenez, Elena Pozzi, Hadis Jameei, Lianne Schmaal, Ilya M Veer, Lea Waller, Neda Jahanshad, Sophia I Thomopoulos, Lauren E Salminen, Miranda Olff, Jessie L Frijling, Dick J Veltman, Saskia B J Koch, Laura Nawijn, Mirjam Van Zuiden, Li Wang, Ye Zhu, Gen Li, Dan J Stein, Jonathan Ipser, Yuval Neria, Xi Zhu, Orren Ravid, Sigal Zilcha-Mano, Amit Lazarov, Jennifer S Stevens, Kerry Ressler, Tanja Jovanovic, Sanne J H Van Rooij, Negar Fani, Sven C Mueller, Anna R Hudson, Judith K Daniels, Anika Sierk, Antje Manthey, Henrik Walter, Nic J A Van Der Wee, Steven J A Van Der Werff, Robert R J M Vermeiren, Christian Schmahl, Julia I Herzog, Ivan Rektor, Pavel Říha, Milissa L Kaufman, Lauren A M Lebois, Justin T Baker, Isabelle M Rosso, Elizabeth A Olson, Anthony King, Israel Liberzon, Michael Angstadt, Nicholas D Davenport, Seth G Disner, Scott R Sponheim, Thomas Straube, David Hofmann, Guangming Lu, Rongfeng Qi, Xin Wang, Austin Kunch, Hong Xie, Yann Quidé, Wissam El-Hage, Shmuel Lissek, Hannah Berg, Steven E Bruce, Josh Cisler, Marisa Ross, Ryan J Herringa, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine Larson, Terri A Deroon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Jeremy Elman, Matthew Panizzon, Carol E Franz, Michael J Lyons, William S Kremen, Brandee Feola, Jennifer U Blackford, Bunmi O Olatunji, Geoffrey May, Steven M Nelson, Evan M Gordon, Chadi G Abdallah, Ruth Lanius, Maria Densmore, Jean Théberge, Richard W J Neufeld, Paul M Thompson, Delin Sun

Faculty, Staff and Students Publications

The increasing scale and complexity of neuroimaging datasets aggregated from multiple study sites present substantial analytic challenges, as existing statistical analysis tools struggle to handle missing voxel-data, suffer from limited computational speed and inefficient memory allocation, and are restricted in the types of statistical designs they are able to model. We introduce Image-Based Meta- & Mega-Analysis (IBMMA), a novel software package implemented in R and Python that provides a unified framework for analyzing diverse neuroimaging features, efficiently handles large-scale datasets through parallel processing, offers flexible statistical modeling options, and properly manages missing voxel-data commonly encountered in multi-site studies. IBMMA successfully …

Ocular Bacterial Microbiome Analysis By Next-Generation Sequencing In Patients With Stevens-Johnson Syndrome And Sjögren’S Disease: Associations With Dry Eye Indices, Luciana Frizon, Talita Trevizani Rocchetti, André Frizon, Rafael Jorge Alves De Alcântara, Ana Luisa Hofling-Lima, Cintia S De Paiva, José Álvaro Pereira Gomes

Faculty, Staff and Students Publications

The ocular surface microbiome plays a crucial role in maintaining immune homeostasis, and its disruption may contribute to mucosal inflammation and autoimmunity. This pilot exploratory study investigated and compared the ocular surface bacterial microbiome in patients with Stevens-Johnson syndrome (SJS), Sjögren's disease (SjD), and healthy controls using next-generation sequencing (NGS) and correlated these findings with dry eye parameters. Conjunctival swabs were collected from sixteen individuals: ten with SJS, three with SjD, and three healthy controls. Dry eye parameters were employed to evaluate the dry eye disease. Microbiome profiles were determined by the NGS of the 16S V3-V4 region and analyzed …

Setdb1 Is Critically Required For Uveal Melanoma Growth And Represents A Promising Therapeutic Target, Imène Krossa, Céline Pisibon, Yann Cheli, Karine Bille, Mélanie Dalmasso, Sabah Hamadat, Chrystel Husser, Marie Irondelle, Julien Cherfils-Vicini, Frédéric Soysouvanh, Sacha Nahon-Esteve, Arnaud Martel, Sandra Lassalle, Jean-Pierre Caujolle, Célia Maschi, Stéphanie Baillif, Dan Hasson, Saul Carcamo, Andrerw E. Aplin, Irwin Davidson, Emily Bernstein, Valeria Naim, Robert Ballotti, Corine Bertolotto, Thomas Strub

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Metastatic uveal melanomas are highly resistant to all existing treatments. To identify actionable vulnerabilities, we conducted a CRISPR-Cas9 knockout screen using a library composed of chromatin regulators. We revealed that the lysine methyltransferase, SETDB1, plays a critical role in metastatic uveal melanoma cell proliferation and survival. Functionally, SETDB1 deficiency induces a DNA damage response, senescence-like state and growth arrest. Knockdown of SETDB1 is associated with a decreased expression of genes related to replication and cell cycle. Moreover, deficiency in CDC6, an essential regulator of DNA replication, phenocopies SETDB1 inhibition. Using a pre-clinical model, we further demonstrated that anti-SETDB1 therapy impairs …

Cerebellar Dysfunction In Glaucoma Patients, Anisha Kasi, Ji Won Bang, Vivek Trivedi, Jeannie Au, Ian Conner, Gadi Wollstein, Joel Schuman, Rakie Cham, Kevin Chan

Wills Eye Hospital Papers

Glaucoma patients often have higher injurious fall rates compared to healthy older adults. However, little is known about the underlying neural mechanisms. Recent evidence shows cerebral changes beyond the visual pathway of glaucoma patients, yet it remains unclear whether the cerebellum, which plays an important role in balance and motor control, is involved in glaucoma. In this study, we sought to investigate cerebellar functional connectivity changes in glaucoma by comparing 32 glaucoma subjects and 10 age-matched healthy control subjects who underwent resting-state functional magnetic resonance imaging at 3 Tesla with eyes closed. After conducting both regions-of-interest and seed-to-voxel analyses, we …

Digital Quality Measure Of Potentially Avoidable Emergency Presentations Among Patients With Colorectal Cancer, Natalia Khalaf, Basim Ali, Andrew Zimolzak, Yan Liu, Li Wei, Fasiha Kanwal, Hardeep Singh

Faculty, Staff and Students Publications

Background: We previously developed a digital quality measure (dQM) of emergency presentations (EPs) in colorectal cancer (CRC) and found it to be associated with worse outcomes. Potentially avoidable EPs were common in this cohort, but identifying them required time-intensive chart reviews. We aimed to enhance the existing dQM to automate the detection of potentially avoidable EPs.

Materials and methods: We defined potentially avoidable EPs as those preceded by a CRC red flag (iron-deficiency anaemia or haematochezia ≥60 days prior, or positive stool-based screening test ≥180 days prior). The enhanced dQM was applied to a national cohort of incident CRC cases …

Aging Affects Lipid Homeostasis In Lacrimal Glands By Upregulating Lipogenesis And Changing Its Specificity, Seher Yuksel, Prashant Kumar, Sydney E Krenz, Kaitlin K Scholand, Zhiyuan Yu, Anastasiia Ivanova, Helen P Makarenkova, Sarah F Hamm-Alvarez, Igor A Butovich, Cintia S De Paiva

Faculty, Staff and Students Publications

Purpose: The lacrimal gland (LG) develops age-related alterations. This study investigated the lipid content of the accumulated secretions within the murine aged LG.

Methods: C57BL/6J animals of different ages (3 months, 12 months, and 20-26 months) were used. Published data of bulk RNA sequencing of aged LGs were used to investigate lipid pathways. Exorbital LGs were excised for histology or PCR. Histologic sections were stained with standard histochemical stains or immunostained using anti-adiponectin, anti-perilipin 2 antibodies, and BODIPY dye. LG lipidomes were investigated using unbiased, untargeted high-resolution liquid chromatography/mass spectrometry (LC/MS), and the data were processed using unbiased, untargeted principal …

Corneal Sensory Nerve Regulation Of Tear Production Through Stimulation Of Transient Receptor Potential Melastatin 8 (Trpm8) Channel: A Potential New Approach For Treating Dry Eye Disease, Juana Gallar, Stephen Pflugfelder, Anat Galor, Preeya K Gupta, Pedram Hamrah

Faculty, Staff and Students Publications

The lacrimal functional unit (LFU) tightly controls the secretion of all tear components, thus playing a critical role in maintaining ocular surface homeostasis. Forming an exquisitely sensitive neural network across the ocular surface, corneal sensory nerves detect environmental stimuli (e.g., temperature, chemicals, and mechanical pressure) through transient receptor potential (TRP) ion channels. Among these, TRP melastatin 8 (TRPM8) is a key regulator of basal tear production. Stimulated by the small temperature reductions and tear film osmolarity increases that arise due to evaporative cooling, TRPM8 activates the LFU, leading to increased basal tear production. Here, we focus on reviewing the topical …

Approach To Ophthalmic Surgery Involving The Anterior Vitreous: A Clinical Practice Update From The American Society Of Retina Specialists, Matthew R Starr, Christina Y Weng, Lejla Vajzovic, Kevin J Blinder, Judy E Kim, J Michael Jumper

Faculty, Staff and Students Publications

When encountering diseases of the anterior vitreous and peripheral retina (ie, the "middle segment" of the eye), vitreoretinal (VR) surgeons are specifically trained in surgical techniques for managing the vitreous and visualizing the peripheral retina during anterior vitrectomy, and therefore they are well equipped to address the complications of surgery involving the anterior vitreous space. This clinical update reviews and compares the current literature discussing techniques and patient outcomes related to complete pars plana vitrectomy versus incomplete, subtotal pars plana vitrectomy, and addresses the proposition of developing an abridged training curriculum for non-VR surgeons to acquire the knowledge and skills …

The Impact Of Myopia On Regional Visual Field Loss And Progression In Glaucoma, Anagha Lokhande, Luo Song, Yueyin Pang, Yan Luo, Louis R. Pasquale, Sarah R. Wellik, Carlos G. De Moraes, Jonathan S. Myers, Mohammad Eslami, Tobias Elze, Lucy Q. Shen, Nazlee Zebardast, David S. Friedman, Michael V. Boland, Mengyu Wang

Wills Eye Hospital Papers

PURPOSE: The purpose of this study was to investigate the impact of myopia on regional visual field (VF) loss and progression in glaucoma.

METHODS: We included 112,633 24-2 VFs; longitudinal analyses comprised patients with at least 5 reliable VFs over 4 years. The degree of myopia was measured by spherical equivalent (SE) extracted from VF testing. Linear and Cox regressions determined the impact of myopia on regional VF loss and progression, respectively. We calculated three VF progression outcomes: (1) mean deviation (MD) progression: MD slope < 0; (2) total deviation (TD) pointwise progression: at least 3 TD locations with TD slope ≤-1 decibels (dB)/year; (3) MD fast progression: MD slope ≤-1 dB/year (P value < 0.05). Longitudinal analyses were conducted for all subjects and with exclusion of patients with high myopia (SE ≤-6.00 diopters [D]).

RESULTS: More negative SE values were associated with worse TD values in the paracentral VF …

The Microenvironment Of Ocular Surface In Keratoconus: A Systematic Review, Sana Niazi, Farideh Doroodgar, Stephen Pflugfelder, Kia Bayat, Seyed-Farzad Mohammadi, Maedeh Mazloomi, Jorge L Alió Del Barrio, Majid Moshirfar, Jorge L Alió

Faculty, Staff and Students Publications

Purpose: Keratoconus is a progressive corneal ectatic disorder characterized by thinning and irregularity of the cornea, significantly impairing visual acuity. Recent studies have explored how non-ectatic conditions, such as dry eye and tear film instability and alteration of the ocular surface microenvironment, contribute to the development and progression of keratoconus. This comprehensive review aims to investigate the complex relationship between keratoconus and ocular surface diseases by examining the microenvironmental changes that occur on the ocular surface throughout the course of keratoconus, as well as the related clinical implications.

Methods: In this PROSPERO-registered study (ID: CRD42025643808), PubMed, Scopus, Cochrane, Embase, Web …

Ocular Blood Flow And Retinal Vascular Reactivity In Alzheimer’S Disease: A Systematic Review Of Retinal Images, Tori Sayers, Alexa Nichols, Amin Ibrahim, Igor Zwir, Andrew Tsin, Lorena Flores-Hernandez, Gladys E. Maestre, Jesus D. Melgarejo

Research Colloquium

Background: Alzheimer’s disease (AD) is the most common form of dementia and one of the leading causes of disability and death in the United States¹. Research efforts aim to identify pathological changes that may help support earlier detection of AD and lead to more accessible tools for monitoring disease progression². The retina is being explored as a potential non-invasive marker of AD, reflecting the shared embryology and microvasculature features between the retina and the brain. Although research has focused on structural changes in retinal vessel diameters and density, few studies have evaluated functional markers of retinal …

Systemic Vascular Dysregulation And Retinal Microvascular Alterations In Glaucoma, Amin Ibrahim, Tori Sayers, Alexa Nichols, Igor Zwir, Andrew Tsin, Lorena Flores-Hernandez, Gladys E. Maestre, Jesus D. Melgarejo

Research Colloquium

Background: Glaucoma is a multifactorial, progressive optic neuropathy, for which both mechanical and vascular mechanisms of pathogenesis have been proposed. Optical coherence tomography angiography (OCTA) enables noninvasive visualization of the choroidal and retinal vasculature and may be used to quantify vascular changes associated with glaucoma. Systemic risk factors, including variations in blood pressure (BP), whether low or elevated, have been associated with the vascular pathogenesis of glaucoma. This systematic review aims to synthesize the current evidence on the relationship between systemic vascular dysregulation and OCTA-derived retinal vascular markers in glaucomatous eyes.

Methods: Following PRISMA guidelines, we conducted a systematic search …

Generation Of Induced Pluripotent Stem Cell Lines (Rfsci003-A, Rfsci004-A) From Monozygotic Twins Discordant For Age-Related Macular Degeneration, Naresh Rajendran, Wendy Runyon, Sam Hu, Ajeet Singh, Rinki Ratnapriya, Ritu Kumar, Karl Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Age-related macular degeneration (AMD) has significant genetic component, yet monozygotic twins frequently exhibit discordance in disease status, highlighting the role of non-genetic factors. To enable comparative studies of AMD pathogenesis, we generated two induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) of a monozygotic twin pair discordant for AMD. These iPSC lines offer a unique genetically matched resource to investigate molecular differences between affected and unaffected twins, as well as their responses to genetic, epigenetic, and environmental contributors to AMD development.

Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu

Mako: NSU Undergraduate Student Journal

Many preoperative and postoperative cataract patients struggle with comprehending the use of prescription medication as directed. Language barriers and low health literacy levels are major factors contributing to improper use of prescriptions. To increase patients comprehension, the Fort Lauderdale Eye Institute employed an educational intervention consisting of a live presentation and an instructional video. Results found that 44% of patients were hesitant to ask questions to clinical staff, 32% felt overwhelmed, and nearly 70% lacked confidence in using their prescribed eye drops. Following the intervention, 91% of patients reported increased confidence in their medications, and most indicated that the video …

Non-Isolated Tetralogy Of Fallot (Tof+): Exome Sequencing Efficacy And Phenotypic Expansions, Julia Volpi, Xiaonan Zhao, Nichole Owen, Tia Evans, Muriel Holder-Espinasse, Nayana Lahiri, Eleanor Sherlock, Gemma Poke, Jeroen Breckpot, Koen Devriendt, Bjorn Cools, Alfredo Brusco, Giovanni Battista Ferrero, Enrico Grosso, Pradeep Vasudevan, Sara Loddo, Antonio Novelli, Maria Cristina Digilio, Aafke Engwerda, Marrit Hitzert, Alison Male, Lucy Bownass, Ruth Newbury-Ecob, Zosia Miedzybrodzka, Ruth Armstrong, Sally Ann Lynch, Gunnar Houge, Shiyi Xiong, Seema R Lalani, Jill A Rosenfeld, Pamela N Luna, Chad A Shaw, Daryl A Scott

Faculty, Staff and Students Publications

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect (CHD). TOF may present in isolation or in conjunction with one or more non-cardiac congenital anomalies or neurodevelopmental disorders (TOF+). Uncertainty regarding the efficacy of various genetic testing strategies, and an incomplete understanding of the genetic causes of TOF+, may lead to hesitancy in recommending genetic testing, particularly, clinical exome sequencing (cES). Here, we analyzed cES data from 131 individuals with TOF+. A definitive or probable diagnosis was made for 31 individuals, yielding a diagnostic rate of 23.6% (31/131). One individual received three diagnoses. Commercially available CHD panels …

Generation Of Human Induced Pluripotent Stem Cell Lines From An Age-Related Macular Degeneration Patient With Hyperreflective Foci Overlying Drusen (Rfsci002-A) And An Unaffected Sibling (Rfsci001-A), Adnin Ashrafi, Wendy Runyon, Sam Hu, Ritu Kumar, Timothy Catchpole, Ajeet Singh, Rinki Ratnapriya, Karl G Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Age-related macular degeneration (AMD) is a leading cause of vision loss, driven by retinal pigment epithelium (RPE) and photoreceptor degeneration. A key feature is drusen accumulation between the RPE and Bruch's membrane. In intermediate AMD, hyperreflective foci (HRF)-bright intraretinal lesions visible on optical coherence tomography (OCT) imaging-serve as biomarkers of disease progression. To study HRF mechanisms, we generated induced pluripotent stem cell (iPSC) lines from an AMD patient with HRF overlying drusen (RFSC4) and their unaffected sibling (RFSC3). These iPSC models offer a platform to explore disease mechanisms and develop therapies for AMD.

The Influence Of Ultra-Wide Field Fluorescein Angiography On The Diagnosis And Management Of Diabetic Retinopathy, Nicole K Scripsema, Tala Al-Khaled, Amy Song, Joelle A Hallak, Rawan Allozi, Aziz A Khanifar, Thanos D Papakostas, Christina Y Weng, Ronald C Gentile, J Peter Campbell, Jessica G Lee, Gennady Landa, Felix Y Chau, William F Mieler, Meenakashi Gupta, Amani A Fawzi, Judy E Kim, Jennifer I Lim, Robison Vernon Paul Chan

Faculty, Staff and Students Publications

Purpose: To study the influence of ultra-widefield fluorescein angiography (FA) on the diagnosis and management of diabetic retinopathy (DR).

Methods: Ten experts in DR completed an online survey in which they were asked to diagnose and manage DR cases using different imaging modalities. Experts independently reviewed 20 cases of DR and provided a diagnosis and management plan for each case, first based on ultra-widefield color-free and red-free images alone and again with the corresponding ultra-widefield FA images. Experts were polled on their diagnostic confidence, use of FA in clinical practice, and opinions on the value of ultra-widefield FA. Based on …

Comparative Efficacy Of Current Topical Treatments For Dry Eye Disease: A Review Of Pivotal Clinical Trials Evaluating Corneal Staining Outcomes, Ahmad Fahmy, Masih Ahmed, Stephen Pflugfelder, Anara Serikbaeva, Fang-Wei Tsao

Faculty, Staff and Students Publications

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Contribution Of Pannexin Channels To Afterimage Signals In The Amphibian Retina, Yufei Liu, Nick Libian, Zheng Jiang, Wen Shen

Faculty, Staff and Students Publications

Pannexin 1 (Panx1) forms large-pore, single-membrane channels that connect the intracellular and extracellular environments, permitting the passage of ions and small molecules such as ATP. Panx1 channels are involved in diverse signaling pathways that contribute to various physiological processes, including sensory processing, although their precise mechanisms of action remain incompletely understood. This study reveals a Panx1-mediated mechanism regulating visual signal processing in the amphibian retina. Using immunolabeling and confocal imaging, we localized Panx1 channels in the cone-dominated On-bipolar cells, specifically at both somas and axon terminals. Whole-cell patch-clamp recordings showed that these channels have high permeability to Cl⁻ ions, which …

A Whole-Brain Voxel-Based Analysis Of Structural Abnormalities In Ptsd: An Enigma-Pgc Study, Cheryl R Z See, Shuqing Si, C Lexi Baird, Courtney C Haswell, Ahmed Hussain, Miranda Olff, Dick J Veltman, Jessie L Frijling, Mirjam Van Zuiden, Saskia B J Koch, Laura Nawijn, Li Wang, Ye Zhu, Gen Li, Yuval Neria, Xi Zhu, Benjamin Suarez-Jimenez, Sigal Zilcha-Mano, Amit Lazarov, Jennifer S Stevens, Kerry Ressler, Negar Fani, Tanja Jovanovic, Sanne J H Van Rooij, Milissa L Kaufman, Lauren A M Lebois, Isabelle M Rosso, Elizabeth A Olson, Justin T Baker, Scott R Sponheim, Seth G Disner, Nicholas D Davenport, Amit Etkin, Adi Maron-Katz, Murray B Stein, Martha E Shenton, Dan J Stein, Jonathan Ipser, Sheri-Michelle Koopowitz, Soraya Seedat, Stefan Du Plessis, Leigh L Van Den Heuvel, Shmuel Lissek, Hannah Berg, Thomas Straube, David Hofman, Lee A Baugh, Gina L Forster, Raluca M Simons, Jeffrey S Simons, Vincent A Magnotta, Kelene A Fercho, Xin Wang, Andrew S Cotton, Erin N O'Leary, Hong Xie, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine L Larson, Terri A Deroon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Jennifer Urbano Blackford, Bunmi O Olatunji, Evan M Gordon, Geoffrey May, Steven M Nelson, Ruth Lanius, Jean Théberge, Maria Densmore, Richard W J Neufeld, Chadi G Abdallah, Christopher L Averill, Ilan Harpaz-Rotem, Ifat Levy, John H Krystal, Elbert Geuze, Remko Van Lutterveld, Emily L Dennis, David F Tate, David X Cifu, William C Walker, Elisabeth A Wilde, Nic J A Van Der Wee, Robert R J M Vermeiren, Steven J A Van Der Werff, Katie Mclaughlin, Kelly Sambrook, Matthew Peverill, Joaquim Radua, Lauren E Salminen, Neda Jahanshad, Sophia I Thomopoulos, Anthony James, Lucia Valmaggia, Paul M Thompson, Rajendra A Morey, Matthew J Kempton

Faculty, Staff and Students Publications

Background: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

Methods: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and …

Consideration Of Patient Phenotypes In Geographic Atrophy Due To Age-Related Macular Degeneration, Rishi P Singh, Christina Y Weng, John W Kitchens, Jaclyn Quilantan, Roy Schwartz, Caroline R Baumal, Roger A Goldberg

Faculty, Staff and Students Publications

Geographic atrophy (GA) is a form of advanced age-related macular degeneration (AMD) affecting approximately 1 million people in the USA and 5 million globally. In this review, retinal imaging techniques used for diagnosis and monitoring progression of GA in AMD, and the risk factors associated with the development and progression of GA are summarised. To familiarise clinicians with common phenotypes of patients with GA, the clinical and imaging features that may lead to rapid progression of GA in various phenotypes are highlighted. With the recent US Food and Drug Administration approval of new GA treatments that reduce lesion growth, understanding …

Identification Of A Translatable Animal Model For Dry Eye Disease Using Comparative Analysis Of Tear Proteins Across Species, Mayelín Pérez-Perdomo, Ana González-López, Laura Ortega-Llamas, David Alba-Molina, Mario Blanco-Blanco, María Del Mar Granados, Adrián Guerrero-Moreno, Stephen Carl Pflugfelder, Christoph Ullmer, Sascha Fauser, Yolanda Jiménez-Gómez, Miguel González-Andrades

Faculty, Staff and Students Publications

Purpose: This study aimed to assess the similarity of tear proteins between experimental animals and humans to identify the most translational animal model for dry eye disease (DED).

Methods: Eleven species were selected for a structural and physicochemical comparison of healthy human tear fluid proteins involved in DED. Amino acid sequences were compared using BLAST. Protein primary structure, isoelectric point (pI) and grand average of hydropathicity (GRAVY) were determined using ExPASy and compared with humans.

Results: Among non-primate mammals, the cat (69.7 %) and pig (68.7 %) showed the highest protein sequence similarity to humans. The ruminants and cat showed …